An antioxidant is a synthetic or natural compound capable of
slowing or preventing the oxidation of other molecules. Most commercial
food antioxidants work by scavenging free radicals or chelating metals.
It is well-known that oxidation damages various biological substances
and subsequently causes many health problems, such as cancer, liver
disease, Alzheimer's disease, aging, arthritis, inflammation,
diabetes, Parkinson's disease, atherosclerosis and AIDS. As a
result, many antioxidant compounds have been used to prevent oxidative
damage.

"You name it, if it's an antioxidant, we'll swallow
it by the bucket-load." This was the overwhelming attitude among
consumers toward antioxidant-rich foods and beverages even a few years
back (New Scientist, 2006). The traditional "trio" of
antioxidants (ascorbate, beta-carotene and alpha-tocopherol) has
received bad press recently, however. Several recent human intervention
trials have demonstrated mostly negative results, and some meta-analyses
and other studies suggested some of these agents not only fail to
protect against disease, but may also accelerate development of cancer
or cardiovascular diseases. This prospect obviously raised concern about
the century-old perceived health benefits of antioxidants.

Antioxidant Market

The global market for antioxidants is growing at a considerable
rate (at a CAGR of 4.71% over the period of 2013-2018) with rapid growth
in the Asia-Pacific and North America markets (TechNavio, 2014). Europe
represents the largest regional market for antioxidants with strong
growth in the U.K. and Ireland. The global market for antioxidants is
segmented into two major types: natural and synthetic. Based on
functions, antioxidants are segmented into functional food ingredients
and products used for preservation.

Combining top antioxidant ingredient sales such as green tea, dark
chocolate, superfruit juice and dietary supplements, Euromonitor
estimated the combined global sales in these categories totaled $34
billion in 2010. According to Euromonitor, the top antioxidant markets
are Japan, the U.S. and China, with sales growing steadily in all five
ranked product areas in the past five years. Growth from 2005 to 2010
was 43% in current terms. As a point of comparison, the global organic
packaged food and beverage market was only $27 billion.

The Antioxidant Controversy

Antioxidant research and outcomes have generated more controversial
opinions than any other scientific subjects. The topic is being
discussed not only in the scientific literature but also in the
mainstream media. A Google search combining the words
"antioxidant" and "health" yields more than 82
million hits, exemplifying the popularity of the subject. These
controversies inevitably hamper research in the field and confuse both
scientists and consumers, generating a wide range of misconceptions.
Bast & Haenen (TIPS, 2013) documented these misconceptions nicely:

* Antioxidants cure any disease

* Antioxidants increase mortality

* The more the better

* At high doses, antioxidants become pro-oxidant

* Any antioxidant will do

* Theoretically, antioxidants cannot behave as such

* Antioxidant status measures health

* Once used, antioxidants are inactive

* Natural antioxidants are superior

* Antioxidant drugs do not work

Perception & Marketing

Product differentiation is the centerpiece of a successful campaign
to win over better-educated, cost-conscious consumers in today's
crowded market. Baby Boomers are mostly affluent and well educated and
are willing to spend on health maintenance and improvement through
nutrient enhanced foods and dietary supplements. At the same time,
younger people and those trying to sustain a healthy, energetic
lifestyle are also a target for this antioxidant campaign. According to
some estimates, around half of U.S. adults take antioxidant supplements
daily.

To attract consumers, use of the word "antioxidant" on
the label of food products is increasing, and numerous assay methods
have been developed to measure this antioxidant potentiality. For
example, food manufacturers are beginning to use values from assays like
ORAC (oxygen radical absorbance capacity) and DPPH (2,
2'-diphenyl-l-picrylhydrazyl) to emphasize the antioxidant profile
of their products.

However, according to new research from the Department of Food
Science at the University of Massachusetts, basing antioxidant activity
claims on results of basic antioxidant assays such as ORAC and DPPH
could be misleading. The results from the free radical scavenging assays
are not consistent, even confusing at times. Accordingly, data from
these assays should not be used to imply that compounds with high free
radical scavenging capacities are good antioxidants in food systems.
According to study findings, the ORAC results showed that, of the tested
compounds, ferulic acid performed the best, followed by coumaric acid,
propyl gallate, gallic acid and vitamin C (ascorbic acid). On the other
hand, the DPPH for non-polar compounds showed that rosmarinic acid came
out on top, with higher values than butylated hydroxytoluene,
tert-butylhydroquinone and vitamin E.

Behind the Theory

The antioxidant hypothesis implies that all changes associated with
reactive species activity are undesirable and the action of antioxidants
beneficial. It is particularly significant that some dietary compounds
have beneficial activities, which are not direct antioxidant effects
(e.g., glucosinolates) while others (e.g., vitamins C and E, and the
carotenoids), previously recognized only for their classical antioxidant
characteristics, are also being shown to induce other biological
responses. In recent years, several experiments demonstrated that all
reactive species act as signaling molecules in cell function,
proliferation and differentiation, and cell death, altering the over
simplistic "antioxidant theory." Unfortunately, the majority
of data available to support this theory have been obtained from cell
culture and animal experiments and the relevance of these data, obtained
under non-physiological conditions, needs to be reassessed.

Ultimately, antioxidants can't be pinned to one mechanism of
action (i.e., scavenging of radicals), but will be based on
inflammation, immunity and oxidative stress. Future health claims could
focus more on this "trio," which better reflects biological
activity and is more relevant to human disease prevention.

Going Natural

A significant number of studies have shown that fruits and
vegetables promote health, while antioxidant supplements do not. Recent
evidence for health benefits strongly supports the food synergy pattern
rather than for individual foods or food constituents. Several reviews
suggest that although dietary supplements may be beneficial in states of
insufficiency, the safe middle ground for consumption is likely food.

The food synergy concept supports the idea of a variety of dietary
habits and of selecting nutrient-rich foods. Also, food must survive
gastrointestinal digestion and be bioavailable at biologically active
forms to deliver health benefits. The American Heart Association (AHA)
doesn't approve of taking antioxidant vitamin supplements to
improve health, believing natural antioxidant foods are better. The AHA
argues there is no evidence that antioxidant supplements provide
cardiovascular protection.

On the other hand, intense marketing campaigns argue that
antioxidant supplements are beneficial for health. A supplement can help
you obtain a proper antioxidant intake even if you don't get it
with food. Ultimately, it makes sense to include as much antioxidant
foods in the diet as possible. Most fruits are not only a rich
antioxidant source, but are also high in fiber and low in fat.

Regulatory Guidance

In June 2008 the U.S. FDA published guidance to help small
companies comply with the labeling of antioxidant products and high
potency products. The guidance confirmed that describing the level of
antioxidant nutrients present in a food is a nutrient content claim, and
may be used on food labels in conjunction with food regulations (21 CFR
101.54(g)).

However, antioxidant nutrient content claims can only be made if
the nutrients have an established Reference Daily Intakes (RDI), as well
as scientifically recognized antioxidant activity. In order to use a
"high in antioxidants" claim, the food would have to contain
20% or more of the Daily Reference Value (DRV) or RDI per serving. For a
"good source" claim, the food would have to contain between
10-19% of the DRV or RDI per serving. In other countries, such as
Australia, Canada and the EU, there is no antioxidant-specific
regulation. Most of the claims in relation to antioxidants are centered
on nutrient content or nutrient profiling.

Commentary

Today's consumers are not satisfied with a generic antioxidant
benefit unless activity offers proven health benefits through clinical
trials. For example, in 2009 Danone removed its Essensis, an
"inside/out" beauty product that contained borage oil, vitamin
E and green tea-derived antioxidants from the French market. One of the
many reasons for its failure was a lack of clinical research on green
tea's benefits for skin care.

Most marketers have simply touted that antioxidants help protect
the body against oxidative damage caused by free radicals. However,
intense debate continues to surround what constitutes a valid
measurement of antioxidant activity. In the past, ORAC value was the
most frequently cited scientific backing for an antioxidant product. In
reality, ORAC is only one piece of the whole antioxidant puzzle and
there are new, biologically relevant assays that can justify antioxidant
measurement from a scientific point of view.

ORAC is physiologically meaningless; it is strictly a test tube
phenomenon. Since biochemical systems, in relation to oxidative status,
work at a variety of levels or strata, ORAC won't pick up all those
levels. Moreover, water-soluble and lipid-soluble antioxidants are
adding more complexity to this puzzle. Overall, experts predicted it
could take more than a decade before human clinical trials confirm
antioxidants as physiological nutrients with specific effects on organ
tissue, which will substantiate health claims. Meanwhile, experts
suggest "consumers will continue to crave these compounds, in a
variety of forms and applications. Supplying such demand will be in the
hands of the innovators who can grow the category, in spite of the
obstacles that exist today." (Murphy, 2014, Free Radical Biology
and Medicine.)

Take-Away Message

It might be helpful "to stop thinking of antioxidant therapy
as a branch of nutrition and instead view it as a drug discovery and
development program." (Murphy, 2014.) It's scientifically
realistic to look beyond the traditional "antioxidant box" and
possible "to design a molecule with the appropriate chemistry to
selectively decrease the concentration of a defined damaging reactive
species at a specific stage of the pathology within the appropriate
organ/cell/subcellular location, sufficiently to bring about a
clinically significant improvement."

Dilip Ghosh, PhD, FACN

nutriConnect

Dilip Ghosh, PhD, FACN, is director of nutriConnect, based in
Sydney, Australia. He is also professionally involved with Soho Flordis
International, the University of Western Sydney, Australia, and is an
Honorary Ambassador with the Global Harmonization Initiative (GHI). Dr.
Ghosh received his PhD in biomedical science from University of
Calcutta, India. He has been involved in drug-development (both
synthetic and natural) and functional food research and development both
in academic and industry domains. Dr. Ghosh has published more than 60
papers in peer-reviewed journals, and he has authored two recent books,
"Biotechnology in Functional Foods and Nutraceuticals," and
"Innovation in Healthy and Functional Foods," under CRC Press.
His next book, "Clinical Perspective of Functional Foods and
Nutraceuticals" is in press. He can be reached at
dilipghosh@nutriconnect.com.au; www.nutriconnect.com.au.

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